Neurodegenerative diseases are diseases in which cerebral and peripheral nerve cells are damaged by a hereditary factor, an environmental factor, an aging factor and the like. Specifically, they include Parkinson's disease, Alzheimer's disease, triplet repeat disease, amyotrophic lateral sclerosis, polyneuropathy, spinal cord injury, cerebrovascular disorders and the like.
Although a general therapeutic method for these neurodegenerative diseases is a method in which neurotransmitters lost by the injury of nerve cells are supplemented, the diseases for which the therapeutic method is effective are limited to Parkinson's disease, Alzheimer's disease and the like at present. Additionally, the progress of nerve cell death cannot be stopped by the neurotransmitter supplementation method.
Regenerative medicine which regenerates the central nervous system has been investigated from the viewpoint of transplantation, as a therapeutic method for positively recovering the function of dopaminergic neurons which had lost by Parkinson's disease. However, the regenerative medicine has not been generally used due to various problems caused by the use of aborted fetal brain. Additionally, studies have also been conducted on a therapeutic method in which neural stem cells obtained from a fetal brain or ES cells obtained from a human fertilized eggs are mass-cultured in vitro and differentiated into a neuron of interest to use it for transplantation (Stem Cells, 2006, vol. 24, p. 1583-1593; The Journal of Neuroscience, 2005, vol. 25, p. 4694-4705). However, its clinical applications are not in progress since the techniques for accurately differentiating them into the desired neuron have not been established yet; teratomas are formed by undifferentiated cells; and there are problems caused by the use of fetal neural stem cells or human ES cells. Accordingly, a technique in which adult-derived neural stem cells are cultured in vitro and used for transplantation is regarded as a promising technique and search for factors which efficiently accelerate proliferation of neural stem cells is expected (Nature Reviews Neuroscience, 2006, vol. 7, p. 395-406).
As a low molecular compound which promotes proliferation of neural stem cells, for example, Salvianolic acid B (JP2006-76948), hedgehog signal agonists (Journal of Biology, 2002, vol. 1, p. 10), selective serotonin reuptake inhibitors (Science, 2003, vol. 301, p. 805-809; Proceedings of the National Academy of Science of the United States of America, 2006, vol. 103, p. 8233-8238), metabotropic glutamate receptor antagonists (Biochemical and Biophysical Research Communications, 2004, vol. 315, p. 493-496), PPARγ agonists (The Journal of Biological Chemistry, 2006, vol. 281, p. 12673-12681), NMDA agonists (Journal of Cell Science, 2007, vol. 120, p. 1358-1370) and the like have been reported.
On the other hand, as a sterol derivative, the following compounds (1) to (4) are known (see Non-Patent Literatures 1 to 4).
